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HISTORY OF ASPERGILLOSIS
ASPERGILLOSIS 1729 – Fungus Aspergillus first identified and catalogued by Italian biologist/priest Micheli Noticed under microscope the fungi looked like an aspergillum which is used to sprinkle holy water and named the genus after it. 1815 – Aspergillus first observed in birds by Mayer 1842 – British physician John Hughes Bennett discovered first case of pulmonary aspergillosis in Gina Milick humans. Called aspergilloma which means “fungus ball” in the Jennifer Hornick lungs Andraele Reed Tiffany Shugart
HISTORY OF ASPERGILLOSIS TAXONOMY
Many early cases of aspergillosis were found Kingdom: Fungi in patients with tuberculosis or high risk occupations such as pigeon-crammers and Phylum: Ascomycota wig combers Order: Eurotiales Some were invasive but most were Family: Trichocomaceae aspergillomas Genus: Aspergillus 1953 – Rankin described the ability of Aspergillus to cause opportunistic infection in immunocompromised patients 1970 – Histopathology and clinical features of disease described in 98 patients
ETIOLOGY ASPERGILLUS FUMIGATUS Conidios Genus Aspergillus includes over 185 pores species are ~20 species reported to cause infections short ,s 7 are facultatively pathogenic mooth- Aspergillus fumigatus most commonly isolated walled species with Found in 90% of infections conical Widespread in nature shaped Commonly found in soil and compost heaps terminal Can also be found indoors vesicles Thermophilic species (Growth at 40° C and above) http://www.mycology.adelaide.edu.au/gallery/photos/ Angioinvasive aspergillus11.gif
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ASPERGILLUS FUMIGATUS ETIOLOGY
• Grown on Next most commonly isolated species include: Czapek dox A. flavus agar • Culture has a A. niger blue-green A. clavatus surface A. glaucus pigmentation A. nidulans with a suede- A. oryzae, like surface consisting of a A. terreus dense felt of A. ustus conidiophores A. versicolor http://www.mycology.adelaide.edu.au/images/fumigatus1.gif
EPIDEMIOLOGY EPIDEMIOLOGY CONT.
Aspergillosis affects people with the Invasive aspergillosis affects people who are immunosuppressed such as: following: People who have had bone marrow Weakened immune system transplants or solid organ transplants Low white blood cell levels People who are taking high doses of corticosteroids Lung cavities People who undergo chemotherapy for Long-term corticosteroid therapy cancer People who have chronic granulomateous A hospital stay disease Asthma and cystic fibrosis People with advanced AIDS Leukemia patients Tuberculosis patients
EPIDEMIOLOGY CONT. EPIDEMIOLOGY CONT.
Aspergillosis is common in the Aspergillosis occurs: environment and is found world- Soil wide Air, spores are inhaled Food-spices and ground pepper Most people breathe in aspergillus Compost and decaying vegetation spores everyday Grains and crops It is impossible to completely avoid Fire proofing materials breathing in aspergillus spores because Bedding, pillows, carpeting they are ubiquitous Ventilation and air conditioning systems People with compromised immune Dust systems who breathe in the spores acquire infections
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MANIFESTATIONS DISEASE SPECTRUM
Forms of the disease involve: Respiratory Sinuses Cranial Lungs Pre-existing lung cavity Pathologic Pulmonary aspergillosis CNS aspergillosis Clinical Sinonasal aspergillosis Thoracic Initial CT Osteomyelitis Endophthalmitis Endocarditis Renal Abscesses Cutaneous (Burns, post surgical wounds, IV insertion sites) Otomycosis Exogenous endophthalmitis Allergic fungal sinusitis Urinary tract fungus balls
HISTOPATHOLOGY HISTOPATHOLOGY
Tissue reaction in aspergillosis is acute suppurative inflammation with areas of ischemic necrosis The fungus proliferates as septate hyphae 2.5-4.5 µm in diameter Hyphae can be characterized as branching dichotomously (Approx 45° angle) Blood vessel invasion, thrombosis, infarction, and dissemination are common Grocott’s methenamine silver (GMS) stained tissue sections The mortality rate for invasive aspergillosis is showing Aspergillus fumigatus in lung tissue, 50-100% and diagnosis by culutre may take as Note : conidial heads forming in an alveolus. long as 4 weeks. Taken from: http://www.mycology.adelaide.edu.au/ gallery/photos/aspergillus08.gif
PATHOGENESIS PATHOGENESIS
Virulence factors: Host response in normal host (non- A. fumigatus has about 4 virulence factors alone: immunosuppressed) Gliotoxin-inhibits mucociliary system Normal immune system response: Fumagillin
Fumagatin Mucosal barriers – Traps Helvolic acid Macrophages – Phagocytosis Since Aspergillus can be found almost everywhere Neutrophils world-wide, it is primary acquired through the respiratory tract. Kills conidiae and inhibits However, there have been cases of disseminated germination of hyphae disease after skin or gastrointestinal infections.
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PATHOGENESIS PATHOGENESIS
Normal host response can be impaired by a number There are three major ways Aspergillus of factors: involves the lungs: Granulocytopenia Mycetoma (non-invasive) Impaired macrophages/neutropenia Underlying disease impairing immune system IPA Lung destruction Invasive Pumonary Aspergillosis Large numbers/prolonged exposure to organism Allergic Hypersensitivity/allergic response In the immunocompromised: Conidia spores colonize lesions or cavities Hyphae begins to form and grow throughout body
DIAGNOSIS LABORATORY DIAGNOSIS
Clinical Presentations: Radiographic picture Fever Classical CT Scan Cough Serological testing Dyspnea Sputum culture Difficulty breathing Transthoracic needle aspiration Hemoptysis
Coughing up blood Chest Pain
DIAGNOSIS DIAGNOSIS
The most extreme diagnosis is surgical procedures Tissue examination Transbronchial biopsy (TBB) Open lung biopsy CT guided percutaneous lung biopsy
http://www.isradiology.org/tropical_deseases/tmcr/chapter6/ clinical23.htm; Courtesy of the Radiology Library, University of Cape Town, South Africa
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DISEASE MANAGEMENT DISEASE MANAGEMENT
Allergic BronchopulmonaryAspergillosis Aspergilloma and Chronic Pulmonary (ABPA) Aspergillosis Caused by an allergy to the spores of the Fungus caused by the Aspergillous mould Aspergillus moulds. Grows in the lung cavity Commonly effects people with asthma and cystic fibrosis patients. Treatment depends on the symptoms Steroids by aerosol or mouth present Prednisolone Itraconazole Itraconazole Voriconazole An oral antifungal drug Surgery
Amphotercin B
DISEASE MANAGEMENT DISEASE MANAGEMENT
Aspergillus Sinusitis Invasive Aspergillosis Disease occurs in the sinuses Effects people with poor immune systems Fungus can transfer from the lung through the May be associated with long standing blood to the brain and other organs symptoms of runny blocked nose Antifungal Drugs May lead to nasal polyps Voriconazole
Surgical drainage, removal of polyps Caspefungin Local steroids Itraconazole Oral Steroids Amphotericin B Antifungals
CASE STUDY – “SUDDEN DEATH DUE TO DISEASE PREVENTION PULMONARY ASPERGILLOSIS”
This disease commonly effects people with a 35 yr old weak immune system Moderately built and malnourished Avoid medications that may further weaken the immune system. TB patient for a year Avoid forests, grain stores, rotting vegetation, Hemoptysis while traveling in a train. and piles of dead leaves. Was declared dead upon arrival to the Hospitals should have good ventilation hospital. Dust control Same day autopsy was performed. Adequate air flow rate
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CASE STUDY CASE STUDY - SYMPTOMS
External examination Internal examination
Blood stains were Trachea and bronchi present over the oral and contained blood clots. nasal orifices Right sided pleural Clubbing of fingers and internal scarring was toes present. No external injuries Surface of lungs was grayish black with necrotic material. Enlarged lymph nodes. CLUBBING OF FINGERS AND TOES. Pale gastrointestinal Source: Courtesy of Journal of organs filled with blood. Forensic and Legal Medicine
CASE STUDY - DIAGNOSIS CASE STUDY - CONCLUSION
Microscopy It was diagnosed to be a case of old Grocott’s methanamine silver stain fibrocavitatory tuberculosis with (GMS) Aspergillus colonization. Biopsy of the lungs No active TB was present. Autopsy Findings of the lungs Cause of death was as hemorrhage secondary to pulmonary aspergillosis. Dilated bronchioles Alveolar septae showed congested vessels. Edema and hemorrhage
CASE STUDY REFERENCES
"The Aspergillus Website, Fungal Research Trust". July 18, 2009
Bhagavath, Prashantha, et al. "Sudden death due to pulmonary aspergillosis." Journal of Forensic and Legal Medicine 16.1 (2009), 27-30.
“Comparison of multiple typing methods for Aspergillus fumigatus.CrossRef DOI Query." Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases [No Volume/Issue] (2009) [No Pagination].
Fig. 2. Microscopy of the lung with "Doctor Fungus". July 18, 2009
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REFERENCES REFERENCES
6K.Marr, T.Patterson, D.Denning. Aspergillosis Pathogenesis, clinic Nguyen MH. (2007). Use of bronchoalveolar lavage to detect al galactomannan for diagnosis of pulmonary aspergillosis among manifestations, and therapy Infectious Disease Clinics of North nonimmunocompromised hosts. Journal Of Clinical Microbiology, America, Volume 16, Issue 4, Pages 875-894 45(9), 2787. Unknown, (2008, March 27). Centers for Disease Control and Preve "Knowledge Storage". July 18, 2009
QUESTIONS QUESTIONS 1. What species of Aspergillus most commonly 3. In a normal host, which immune defense mechanism causes infections? usually inhibits hyphae germination? A) A. fumigatus A) Mucosal barriers B) Thrombocytes B) A. niger C) Neutrophils C) A. versicolor D) All of the Above D) A. flavus
4. What type of medications should people affected by 2. Aspergillus most commonly affects the: Aspergillus avoid? A) Heart A) Amphotericin B B) Skin B) Any that weaken the immune system C) Lungs C) Anti-depressants D) GI tract D) All above
QUESTIONS
5) What is a virulence factor for Aspergillus fumigatus? A) Fumagillin B) Fumagatin C) Gliotoxin D) All of the above
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